Oral soft tissue plays an important role in the structure and function of the oral cavity by protecting against exogenous substances, pathogens, and mechanical stresses. Repair of oral soft tissue defects that arise as a result of disease, trauma, or congenital abnormalities is often accomplished via transplantation or transfer of autologous mucosal tissue. However, this method of treatment can be complicated by the relatively small amount of autologous mucosal tissue that is available, as well as by the morbidity that may be associated with the donor site and patient reluctance to have oral (eg, palatal) surgery. To circumvent these problems, clinicians have turned to the fields of tissue engineering and regenerative medicine to develop acellular and cellular strategies for regenerating oral soft tissue. This review focuses on the efficacy and safety of cell-based investigational approaches to the regeneration of oral soft tissue.